1-Methylimidazole → ethyl (2R)-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]butan-2-yl (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate

Participants

Reaction Conditions

Reaction Steps

1-Methylimidazole (1.91 mL, 24 mmol) was added to a stirring suspension of ethyl hydrogen (4-{[4-{[6-bromo-2-(methylcarbamoyl)pyridin-3-yl]amino}-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzyl)phosphonate (Compound 38C, 1 g, 2 mmol), (2R)-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]butan-2-ol (Compound 69B, 430 mg, 1.6 mmol) and (benzotriazol-1-yloxy)tripyrrolidino-phosphonium hexafluorophosphate (5.04 g, 9.69 mmol) in 1,2-dichloroethane (49.5 mL). The reaction was allowed to stir at 60° C. for 24 hrs, after which, it was concentrated in vacuo to a solid and purified using a Teledyne ISCO Combiflash® RF system [0-5% MeOH in 1:1 EtOAc/DCM] to afford 442 mg of the desired product as mixture of diastereomers (32%). MS (ESI): m/z=867.78/869.81 [M+H]+. UPLC: tR=1.69 min (UPLC-TOF: polar—2 min)

Provenance & Evidence